Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong Jean

doi:10.1016/j.bbrc.2015.08.098

Cited by 20 publications

(14 citation statements)

References 43 publications

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“…Life span analyses was performed using PRISM 6 (GraphPad, USA) with the Kaplan–Meier method. Comparisons among groups were conducted using Log-rank test 70 .…”

Section: Methodsmentioning

confidence: 99%

Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences

Hong

Choi

2016

Nat Commun

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Genome stability is essential for all organisms. Translationally controlled tumour protein (TCTP) is a conserved protein associated with cancers. TCTP is involved in multiple intracellular functions, but its role in transcription and genome stability is poorly understood. Here, we demonstrate new functions of Drosophila TCTP (Tctp) in transcription and the stability of repeated sequences (rDNA and pericentromeric heterochromatin). Tctp binds Brahma (Brm) chromatin remodeler to negatively modulate its activity. Tctp mutants show abnormally high levels of transcription in a large set of genes and transposons. These defects are ameliorated by brm mutations. Furthermore, Tctp promotes the stability of repeated sequences by opposing the Brm function. Additional regulation of pericentromeric heterochromatin by Tctp is mediated by su(var)3-9 transcriptional regulation. Altogether, Tctp regulates transcription and the stability of repeated sequences by antagonizing excess Brm activity. This study provides insights into broader nuclear TCTP functions for the maintenance of genome stability.

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“…Life span analyses was performed using PRISM 6 (GraphPad, USA) with the Kaplan–Meier method. Comparisons among groups were conducted using Log-rank test 70 .…”

Section: Methodsmentioning

confidence: 99%

Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences

Hong

Choi

2016

Nat Commun

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“…Among others, genes involved in the defense/immune response were both up- and down-regulated. Of the genes known to be involved in life span control, at least two genes associated with increased life span, heat shock protein 26 (hsp26) and NAD-dependent methylenetetrahydrofolate dehydrogenase ( Nmdmc ), increased transcription (Wang et al, 2004 ; Yu et al, 2015 ). It is unclear whether transcription of a similar pool of genes would be affected by a reduction in esg expression or whether the same effects would be observed at other developmental stages and in adults.…”

Section: Discussionmentioning

confidence: 99%

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

et al. 2018

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In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in Drosophila melanogaster. Among other genes, escargot (esg) was demonstrated to be causally associated with an increase in the life span of male flies. Here, we present new data on the role of esg in life span control. We show that esg affects the life spans of both mated and unmated males and females to varying degrees. By analyzing the survival and locomotion of the esg mutants, we demonstrate that esg is involved in the control of aging. We show that increased longevity is caused by decreased esg transcription. In particular, we demonstrate that esg knockdown in the nervous system increased life span, directly establishing the involvement of the neuronal esg function in life span control. Our data invite attention to the mechanisms regulating the esg transcription rate, which is changed by insertions of DNA fragments of different sizes downstream of the structural part of the gene, indicating the direction of further research. Our data agree with the previously made suggestion that alterations in gene expression during development might affect adult lifespan, due to epigenetic patterns inherited in cell lineages or predetermined during the development of the structural and functional properties of the nervous system.

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“…A number of genes within Q4 show expression variation between young and old animals in our study (Additional file 15 : Table S7). This set includes CG8032 , which is also the only member of a set of 39 lifespan-reducing loci identified in a gain-of-function screen that is implicated by QTL mapped in the present study [ 22 ], and Nmdmc , overexpression of which has been shown to extend lifespan in flies [ 81 ]. Given the number of genes within Q4, and the ample evidence of multiple candidates present in the region, it is not unlikely that more than one gene in the region is responsible for the QTL we map.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of variation in lifespan using a multiparental advanced intercross Drosophila mapping population

2016

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BackgroundConsiderable natural variation for lifespan exists within human and animal populations. Genetically dissecting this variation can elucidate the pathways and genes involved in aging, and help uncover the genetic mechanisms underlying risk for age-related diseases. Studying aging in model systems is attractive due to their relatively short lifespan, and the ability to carry out programmed crosses under environmentally-controlled conditions. Here we investigate the genetic architecture of lifespan using the Drosophila Synthetic Population Resource (DSPR), a multiparental advanced intercross mapping population.ResultsWe measured lifespan in females from 805 DSPR lines, mapping five QTL (Quantitative Trait Loci) that each contribute 4–5 % to among-line lifespan variation in the DSPR. Each of these QTL co-localizes with the position of at least one QTL mapped in 13 previous studies of lifespan variation in flies. However, given that these studies implicate >90 % of the genome in the control of lifespan, this level of overlap is unsurprising. DSPR QTL intervals harbor 11–155 protein-coding genes, and we used RNAseq on samples of young and old flies to help resolve pathways affecting lifespan, and identify potentially causative loci present within mapped QTL intervals. Broad age-related patterns of expression revealed by these data recapitulate results from previous work. For example, we see an increase in antimicrobial defense gene expression with age, and a decrease in expression of genes involved in the electron transport chain. Several genes within QTL intervals are highlighted by our RNAseq data, such as Relish, a critical immune response gene, that shows increased expression with age, and UQCR-14, a gene involved in mitochondrial electron transport, that has reduced expression in older flies.ConclusionsThe five QTL we isolate collectively explain a considerable fraction of the genetic variation for female lifespan in the DSPR, and implicate modest numbers of genes. In several cases the candidate loci we highlight reside in biological pathways already implicated in the control of lifespan variation. Thus, our results provide further evidence that functional genetics tests targeting these genes will be fruitful, lead to the identification of natural sequence variants contributing to lifespan variation, and help uncover the mechanisms of aging.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0419-9) contains supplementary material, which is available to authorized users.

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Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

Cited by 20 publications

References 43 publications

Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences

Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

Genetic analysis of variation in lifespan using a multiparental advanced intercross Drosophila mapping population

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